Project III: Hippocampal inhibition and obesity Although specification of physiological substrates will be central to any comprehensive account of food intake regulation, it is now clear that such accounts must also describe the role of learning and memory in the control of eating and appetitive behavior. As noted above, food intake regulation is likely to depend on the ability to inhibit responding to orosensory and other food related stimuli that are associated with rewarding post-ingestive consequences. New data and new interpretations of older findings suggest that this type of inhibitory ability may depend on the hippocampus, a brain structure long implicated as a substrate for learning and memory. Encouraged by a variety of physiological and behavioral evidence, Project III will evaluate the hypothesis that the regulation of food intake (and ultimately body weight) is, at least in part, a hippocampal-dependent function. Of special importance are findings that consumption of diets high in fat and/or processed sugars alters hippocampal neuronal activity and impairs the performance of rats on memory tasks that are thought to rely on hippocampus. These data suggest that dietary factors might contribute to overweight and obesity in humans by interfering with hippocampal-dependent inhibitory processes. Project III will evaluate this possibility in both rats and humans. This project will also study the effects of damage confined to selected regions of the hippocampus (e.g., dorsal, ventral, ventral pole) on intake and body adiposity and on sensitivity to neuropeptide signals that appear to mediate short-term meal termination (e.g., cholecystokinin) and longer term inhibition of feeding behavior (e.g., leptin, insulin). These hippocampal regions differ in terms of their connections to hypothalamic feeding control centers. This project will be directed by Dr. Davidson (PI), Department of Psychological Sciences, at Purdue University, in collaboration with Dr. Leonard Jarrard, Department of Psychology and Neuroscience Program, Washington &Lee University, and Drs. Stephen Benoit and Debra Clegg, Department of Psychiatry, University of Cincinnati Medical School.